Laboratory Simulation of Response to a Shock Environment

The focus of this work will be to simulate a harsh, blast environment on a space structure. Data from a reverse Hopkinson bar (RHB) test is used to generate the response to a symmetric, distributed load. The RHB generates a high-amplitude, high-frequency content, concentrated pulse that excites components at near-blast levels. The transfer functions generated at discrete points, with the RHB, are used to generate an experimental model of the structure, which is then used in conjunction with the known pressure distribution, to estimate the component response to a blast. The shock spectrum of the predicted response and the actual response compared well in two of the three cases presented

Extended calibration of thin-foil manganin gage in ALOX material

The purpose of this program was to extend an existing manganin gage calibration curve, correlating stress as a function of change in gage resistance/gage resistance ({Delta}R/R), and obtain gage repeatability data from stripped manganin thin-foiled gages manufactured by the Measurements Group Inc., Micro-Measurements division. The experiments extended the existing calibration curve range from the current 0.5 GPa to 6.1 GPa by examining impact stresses of 0.1 GPa in the lower range, and 8.0 and 10.0 GPa in the higher range. The manganin gages were embedded in ALOX (42% by volume alumina in EPON 828 epoxy) material. A light gas-gun was used at Sandia National Laboratories Explosive Components Facility (ECF) to drive an impactor material, ALOX or Tungsten, into the ALOX target containing two gages in a centered arrangement. Tilt and velocity of the impactor were measured along with the gage outputs. A total of 11 tests were conducted using the same ALOX target material that was used when obtaining the original calibration curve. Two initial tests were completed using Polymethyl Methacrylate (PMMA) as the impactor and target at an impact pressure of 3.3 GPa for comparison of gage output with analysis and literature values. The installed gage, stripped of its backing, has a nominal thickness of 5 microns. The thin gage and high speed instrumentation allowed higher output resolution measurements than can be obtained with 76 microns manganin wire used previously. The areas of investigation that will be presented include: (1) experimental setup, (2) comparison with existing calibration curve, and (3) discussions of the extended calibration data

Conformations of closed DNA

We examine the conformations of a model for a short segment of closed DNA. The molecule is represented as a cylindrically symmetric elastic rod with a constraint corresponding to a specification of the linking number. We obtain analytic expressions leading to the spatial configuration of a family of solutions representing distortions that interpolate between the circular form of DNA and a figure-eight form that represents the onset of interwinding. We are also able to generate knotted loops. We suggest ways to use our approach to produce other configurations relevant to studies of DNA structure. The stability of the distorted configurations is assessed, along with the effects of fluctuations on the free energy of the various configurations.Comment: 39 pages in REVTEX with 14 eps figures. Submitted to Phys. Rev. E. This manuscript updates, expands and revises, to a considerable extent, a previously posted manuscript, entitled "Conformations of Circular DNA," which appeared as cond-mat/970104

Phase behavior of hydrogen–light-hydrocarbon systems

The decreasing solubility of hydrogen in hydrocarbons with decreasing temperature continues down to the freezing point of the hydrocarbons, around −300°F. This behavior is shown to be an enlargement of phenomena exhibited by normal hydrocarbon mixtures. Methods of predicting equilibrium-phase compositions are presented for hydrogen in ligh-hydrocarbon systems. The correlations are satisfactory for binary and certain ternary systems, but are not reliable for complex mixtures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37292/1/690030219_ftp.pd

Theoretical Analysis of Competing Conformational Transitions in Superhelical DNA

We develop a statistical mechanical model to analyze the competitive behavior of transitions to multiple alternate conformations in a negatively supercoiled DNA molecule of kilobase length and specified base sequence. Since DNA superhelicity topologically couples together the transition behaviors of all base pairs, a unified model is required to analyze all the transitions to which the DNA sequence is susceptible. Here we present a first model of this type. Our numerical approach generalizes the strategy of previously developed algorithms, which studied superhelical transitions to a single alternate conformation. We apply our multi-state model to study the competition between strand separation and B-Z transitions in superhelical DNA. We show this competition to be highly sensitive to temperature and to the imposed level of supercoiling. Comparison of our results with experimental data shows that, when the energetics appropriate to the experimental conditions are used, the competition between these two transitions is accurately captured by our algorithm. We analyze the superhelical competition between B-Z transitions and denaturation around the c-myc oncogene, where both transitions are known to occur when this gene is transcribing. We apply our model to explore the correlation between stress-induced transitions and transcriptional activity in various organisms. In higher eukaryotes we find a strong enhancement of Z-forming regions immediately 5′ to their transcription start sites (TSS), and a depletion of strand separating sites in a broad region around the TSS. The opposite patterns occur around transcript end locations. We also show that susceptibility to each type of transition is different in eukaryotes and prokaryotes. By analyzing a set of untranscribed pseudogenes we show that the Z-susceptibility just downstream of the TSS is not preserved, suggesting it may be under selection pressure

Dynamics of liquid 4He in Vycor

We have measured the dynamic structure factor of liquid 4He in Vycor using neutron inelastic scattering. Well-defined phonon-roton (p-r) excitations are observed in the superfluid phase for all wave vectors 0.3 < Q < 2.15. The p-r energies and lifetimes at low temperature (T = 0.5 K) and their temperature dependence are the same as in bulk liquid 4He. However, the weight of the single p-r component does not scale with the superfluid fraction (SF) as it does in the bulk. In particular, we observe a p-r excitation between T_c = 1.952 K, where SF = 0, and T_(lambda)=2.172 K of the bulk. This suggests, if the p-r excitation intensity scales with the Bose condensate, that there is a separation of the Bose-Einstein condensation temperature and the superfluid transition temperature T_c of 4He in Vycor. We also observe a two-dimensional layer mode near the roton wave vector. Its dispersion is consistent with specific heat and SF measurements and with layer modes observed on graphite surfaces.Comment: 3 pages, 4 figure

UK Environmental Change Network stakeholder consultation

During the Environmental Change Network (ECN) site mangers meeting feedback on the role of UK-SCAPE funding was sought. Representatives from collaborating institutions did not restrict their comments to only the period of UK-SCAPE, as this program is a continuation of previous national capability funding. The stakeholders present appreciated the role of UKCEH through the processes of co-design, co-delivery and co-development in shaping the ECN. They further commented on the co-dependency conferred by the network for their institutions and sites. While several stakeholders noted that they could not benefit directly from UK-SCAPE funding they recognised that funding was required for coordination of the network in addition to collecting monitoring data. They highlighted the risk of failure of the network and the lost opportunities in terms of collaborative working and data delivery to the research community if funding is not maintained in the network

The UK Environmental Change Network datasets – integrated and co-located data for long-term environmental research (1993–2015)

Long-term datasets of integrated environmental variables, co-located together, are relatively rare. The UK Environmental Change Network (ECN) was launched in 1992 and provides the UK with its only long-term integrated environmental monitoring and research network for the assessment of the causes and consequences of environmental change. Measurements, covering a wide range of physical, chemical, and biological “driver” and “response” variables are made in close proximity at ECN terrestrial sites using protocols incorporating standard quality control procedures. This paper describes the datasets (there are 19 published ECN datasets) for these co-located measurements, containing over 20 years of data (1993–2015). The data and supporting documentation are freely available from the NERC Environmental Information Data Centre under the terms of the Open Government Licence (see paper for DOIs)

WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice

Improved understanding of the molecular mechanisms underlying dysregulated inflammatory responses in severe infection and septic shock is urgently needed to improve patient management and identify new therapeutic opportunities. The WNT signaling pathway has been implicated as a novel constituent of the immune response to infection, but its contribution to the host response in septic shock is unknown. Although individual WNT proteins have been ascribed pro- or anti-inflammatory functions, their concerted contributions to inflammation in vivo remain to be clearly defined. Here we report differential expression of multiple WNT ligands in whole blood of patients with septic shock and reveal significant correlations with inflammatory cytokines. Systemic challenge of mice with lipopolysaccharide (LPS) similarly elicited differential expression of multiple WNT ligands with correlations between WNT and cytokine expression that partially overlap with the findings in human blood. Molecular regulators of WNT expression during microbial encounter in vivo are largely unexplored. Analyses in gene-deficient mice revealed differential contributions of Toll-like receptor signaling adaptors, a positive role for tumor necrosis factor, but a negative regulatory role for interleukin (IL)-12/23p40 in the LPS-induced expression of Wnt5b, Wnt10a, Wnt10b, and Wnt11. Pharmacologic targeting of bottlenecks of the WNT network, WNT acylation and β-catenin activity, diminished IL-6, tumor necrosis factor, and IL-12/23p40 in serum of LPS-challenged mice and cultured splenocytes, whereas IL-10 production remained largely unaffected. Taken together, our data support the conclusion that the concerted action of WNT proteins during severe infection and septic shock promotes inflammation, and that this is, at least in part, mediated by WNT/β-catenin signaling

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes